1. Field of the Invention
The present invention relates to ω-silanyl-n-alkanal compounds, to their process of preparation, to their use for the functionalization of solid supports, to the solid supports functionalized by these compounds and to the use of the solid supports thus functionalized for immobilization and/or synthesis of advantageous biological molecules.
2. Description of the Background Art
In order to carry out chemical syntheses or to immobilize advantageous biological molecules, such as nucleic acids, proteins or cell ligands, at the surface of a solid support (biochips), it is first of all necessary to graft, to the surface, coupling agents which will provide for the attachment of the organic molecules to the support.
The most commonly mentioned limitations in the preparation and the use of biochips and in particular of DNA biochips are the accessibility of the linking functional groups and the loss of selectivity due in particular to a change in the organic or inorganic interface, whether this is at the time of hybridization or else during the various rinsing stages, optionally during the recycling of the microsupport.
The synthetic scheme for the grafting of the molecules of oligonucleotides to the solid support presupposes the pretreatment of the surfaces (generally oxides or metals) with a coupling agent comprising a functional ending which will become arranged at the surface of the material.
Self-Assembled Monolayers (SAMs) are defined as an assemblage of molecules in which the molecules are arranged, which arrangement is due to interactions between the chains of the molecules, giving rise to a stable, monomolecular and well-ordered anisotropic film (A. Ulman, Chem. Rev., 1996, 96, 1533-1554). These self-assembled monolayers, which can be obtained reproducibly (J. B. Brozska et al., Langmuir, 1994, 10, 4367-4373), have the distinguishing feature for forming a dense and homogeneous film which is resistant to chemical treatments (acidic or basic chemical treatments). They are generally obtained from thiols, carboxylic acids or organosilicon compounds (also referred to as organofunctional silanes).
Organofunctional silanes are compounds which are particularly well suited to modifying surfaces of siliceous substrates. For example, they are used industrially as adhesion promoters (or coupling agents) by creating a molecular bridge between organic polymers and the oxide, resulting in composite materials.
Various organosilicon compounds have thus already been used as coupling agents for the functionalization of solid supports (L. A. Chrisey et al., Nucleic Acids Research, 1996, 24, 15, 3031-3039, U. Maskos et al., Nucleic Acids Research, 1992, 20, 7, 1679-1684) for the purpose of immobilizing or synthesizing in situ oligonucleotides. However, the organosilicon coupling agents used in these studies form nonhomogeneous films which show very little resistance to subsequent chemical treatments for the synthesis or immobilization of oligonucleotides. Furthermore, the formation of the films with these coupling agents is not reproducible.
The coupling agent properties of a silane depend on the nature of the organic R group but they depend in particular on the method of attachment to the surface via X functional groups. Thus, polyfunctional silanes of RSiX3 and R2SiX2 type, that is to say comprising three or two linking functional groups, not only hang on to the surface of the solid support but can also react with one another to form a crosslinked layer. In contrast, monofunctional silanes of R3SiX type, that is to say comprising only a single linking functional group, only get to hang on individually to the substrate.
The organosilanes RSiX3 and R3SiX have been the most widely studied in the literature, both from the academic viewpoint and from the industrial viewpoint, the first organosilanes because they result in the formation of a tridimensional network and the second organosilanes because they make it possible to determine the number of silanol sites present at the surface. The functional groups generally studied are the Si—Cl, Si—OMe and Si—OEt bonds and a classic example of surface modification with a trichlorosilane is given in Scheme A below:

However, the use of these trichlorosilanes requires an additional stage, after grafting to the surface, of activation of the free bond in order to make possible the reaction with an amino group (NH2) of a biological molecule. By way of example, when the grafted silane comprises an end epoxide functional group, the latter subsequently has to be activated according to a process employing two stages (a stage of opening the epoxide ring by hydrolysis, followed by an oxidation stage) in order to result in the corresponding reactive aldehyde functional group.
However, it is not always acceptable from an industrial viewpoint to carry out additional stages of activation of the end functional groups of the silanes in order to make possible the subsequent covalent attachment of biological molecules carrying a complementary functional group and to do so can have negative consequences with regard to the quality of the support finally obtained (loss of selectivity due in particular to a change in the organic/inorganic interface, poor distribution of the linking functional groups, and the like).